CD58

Summary

CD58 (CD58 molecule, HGNC:1688) is a protein-coding gene on chromosome 1p13.1, encoding Lymphocyte function-associated antigen 3 (P19256). Ligand of the T-lymphocyte CD2 glycoprotein.

This gene encodes a member of the immunoglobulin superfamily. The encoded protein is a ligand of the T lymphocyte CD2 protein, and functions in adhesion and activation of T lymphocytes. The protein is localized to the plasma membrane. Alternatively spliced transcript variants have been described.

Source: NCBI Gene 965 — RefSeq curated summary.

At a glance

• GWAS associations: 12
• Clinical variants (ClinVar): 50 total
• Druggable target: yes
• Cancer driver (intOGen): loss-of-function (tumor-suppressor-like) across 2 cancer types
• MANE Select transcript: NM_001779

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1688
Approved symbol	CD58
Name	CD58 molecule
Location	1p13.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000116815
Ensembl biotype	protein_coding
OMIM	153420
Entrez	965

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 5 protein_coding, 1 nonsense_mediated_decay

ENST00000369487, ENST00000369489, ENST00000457047, ENST00000464088, ENST00000526981, ENST00000907570

RefSeq mRNA: 2 — MANE Select: NM_001779 NM_001144822, NM_001779

CCDS: CCDS44199, CCDS888

Canonical transcript exons

ENST00000369489 — 6 exons

Exon	Start	End
ENSE00000913430	116521906	116521983
ENSE00000957938	116535965	116536228
ENSE00001158370	116544311	116544604
ENSE00001728169	116514534	116514822
ENSE00001764892	116570903	116571026
ENSE00003791378	116519231	116519267

Expression profiles

Bgee: expression breadth ubiquitous, 278 present calls, max score 95.94.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 48.8716 / max 1871.3983, expressed in 1818 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
14015	48.8716	1818

Top tissues by expression

294 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
jejunal mucosa	UBERON:0000399	95.94	gold quality
monocyte	CL:0000576	95.45	gold quality
right lung	UBERON:0002167	95.41	gold quality
mononuclear cell	CL:0000842	95.21	gold quality
mucosa of sigmoid colon	UBERON:0004993	95.06	gold quality
leukocyte	CL:0000738	94.95	gold quality
heart right ventricle	UBERON:0002080	94.78	gold quality
colonic mucosa	UBERON:0000317	94.54	gold quality
periodontal ligament	UBERON:0008266	93.37	gold quality
calcaneal tendon	UBERON:0003701	93.20	gold quality
palpebral conjunctiva	UBERON:0001812	93.14	gold quality
bone marrow	UBERON:0002371	92.99	gold quality
rectum	UBERON:0001052	92.78	gold quality
duodenum	UBERON:0002114	92.78	gold quality
granulocyte	CL:0000094	92.70	gold quality
myocardium	UBERON:0002349	92.52	gold quality
right coronary artery	UBERON:0001625	92.43	gold quality
left ventricle myocardium	UBERON:0006566	92.40	gold quality
thoracic aorta	UBERON:0001515	92.16	gold quality
blood	UBERON:0000178	92.15	gold quality
cardiac ventricle	UBERON:0002082	92.14	gold quality
ascending aorta	UBERON:0001496	92.13	gold quality
left coronary artery	UBERON:0001626	92.13	gold quality
heart left ventricle	UBERON:0002084	92.13	gold quality
descending thoracic aorta	UBERON:0002345	92.09	gold quality
lower esophagus mucosa	UBERON:0035834	92.07	gold quality
trabecular bone tissue	UBERON:0002483	92.05	gold quality
cartilage tissue	UBERON:0002418	91.81	gold quality
heart	UBERON:0000948	91.56	gold quality
lower lobe of lung	UBERON:0008949	91.49	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): NFKB1, NFKBIA, RELA, SPI1, TP53

miRNA regulators (miRDB)

21 targeting CD58, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-3119	99.92	71.34	2390
HSA-MIR-6844	99.82	70.69	2423
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-8084	99.73	69.57	1760
HSA-MIR-4699-3P	99.71	70.15	3142
HSA-MIR-4677-5P	99.70	70.09	1940
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-545-5P	99.66	70.18	2308
HSA-MIR-3177-5P	99.65	70.38	1174
HSA-MIR-888-3P	99.53	69.77	1057
HSA-MIR-32-3P	99.36	68.20	2517
HSA-MIR-888-5P	99.30	70.15	1855
HSA-MIR-2054	99.20	68.89	1699
HSA-MIR-581	98.39	67.42	835
HSA-MIR-4727-3P	96.75	64.97	415

Literature-anchored findings (GeneRIF, showing 40)

• Here, the authors provide evidence that the microRNA, miR-965, acts via string and wingless to control histoblast proliferation and migration. (PMID:26226636)
• CD2-CD58 binding site (PMID:11575926)
• Signal-dependent adhesion of resting NK cells initiated by expression of ICAM-1 is greatly enhanced by coexpression of LFA-3, even in the absence of cytokines. (PMID:12496412)
• The complement inhibitor CD59 and the lymphocyte function-associated antigen-3 (LFA-3, CD58) genes possess functional binding sites for the p53 tumor suppressor protein. (PMID:12553064)
• Transmembrane CD58 may trigger signaling independently of the GPI-linked isoform. (PMID:15093607)
• Human cells transformed with Ad12 demonstrated reduced expression of cell surface LFA-3. (PMID:15963548)
• The level of CD58 molecule (in both serum and PBMC form) of patients with hepatitis B is related to the degree of liver damage. (PMID:16830383)
• We use this analysis to determine that the 2D Kd for CD2-CD58 is 5.4-7.6 molecules/microm2. 2D Kd analysis provides a general and quantitative measure of the mechanisms regulating cell-cell adhesion. (PMID:17085486)
• T cell activation causes the CD58-bound CD2 to be recognized and immobilized at sites of cell-cell contact, thereby strengthening T cell-APC adhesion (PMID:17168569)
• Susceptibility gene for multiple sclerosis in Australians. (PMID:18650830)
• We found variable, but persistently elevated levels of sLFA-3 throughout the various phases and types of the hemorrhagic fever with renal syndrome, which suggest that sLFA-3 levels have correlation with disease stages. (PMID:18820826)
• the synergistic synthesis of IL-8 occurs when lymphocytes are stimulated through the CD2 pathway by CD58 on HT-29 cells, resulting in TNF-alpha release that, in turn, augments IL-8 synthesis and CD58 expression by the HT-29 cells (PMID:19109405)
• during clinical remission, increases in CD58 expression, mediated by the protective allele, up-regulate the expression of FoxP3 through engagement of the CD58 receptor, CD2, leading to the enhanced function of TREG cells that are defective in MS (PMID:19237575)
• Cross-linking of CD58 induces protein tyrosine phosphorylation of BLNK, Syk and PLCgamma, and activation of ERK and Akt/PKB. (PMID:19268704)
• Study reports additional genetic and transcriptomic evidence for the role of CD58 (LFA-3) in multiple sclerosis (MS) susceptibility using a Swedish case-control material, with a result that closely mimics that of De Jager et al. (PMID:19497873)
• Studies indicate that five SNPs showed genome-wide significant association with MS: HLA-DRA, IL7R, IL2RA, CD58 and CLEC16A. (PMID:19834503)
• Genetic variants at CD58, is associated with rheumatoid arthritis risk (PMID:19898481)
• Studies indicate that SNP in IL7RA, IL2RA, CD58 and CLEC16A genes has been consistently associated with MS. (PMID:20450971)
• Data show that coculture with activated T cells upregulated expression of CD54 and CD58 and secretion of galectin-1 by MSCs. (PMID:20570633)
• Two large cohorts of systemic sclerosis (SSc) patients of European Caucasian ancestry do not support the implication of ITGAM, ITGAX, and CD58 genes in the genetic susceptibility of SSc, although they were identified as autoimmune disease risk genes. (PMID:21362770)
• Seven selected CD58 single-nucleotide polymorphisms were found to not affect aspirin-exacerbated respiratory disease susceptibility in a Korean population. (PMID:21726122)
• In 21 percent of diffuse large B cell lymphoma cases, lesions involve the CD58 gene, which encodes a molecule involved in T and natural killer cell-mediated responses (PMID:22137796)
• Genetic variations in CD58 were associated with the susceptibility of neuromyelitis optica in a Korean population. (PMID:24655566)
• Results indicate that CD58 is a novel cell-surface marker that functionally regulates self-renewal of Colorectal tumor-initiating cells. (PMID:24727892)
• SNPs in CD58 are associated with increased risk of candidemia. (PMID:25197941)
• Linkage disequilibrium show evidence that mir-548ac rs1414273 variant is strongly associated with Multiple sclerosis (MS)-associated haplotype and confirms the single nucleotide polymorphisms within the first intron of CD58 been related too. [review] (PMID:25795118)
• The positive correlation is established between content of polymorphic nuclear monocytes and level of expression of molecules of LFA-1, ICAM-1, LFA-3, and PECAM-1. (PMID:25884075)
• This study demonstrated that the Polymorphism, Single Nucleotide of CD58 is associated with multiple sclerosis in man in Russia. (PMID:25903733)
• the fundamental mechanism of glycosylation of human CD2 is to promote CD2-CD58 binding by conformational adjustment of CD2 (PMID:25984915)
• CD58/CD2 is the primary costimulatory pathway in human CD28-CD8+ T cells. (PMID:26041540)
• Cytometry analysis evidenced a specific expression profile on reticulocytes of SCA infants, with notably an increased expression of the adhesion molecules Lu/BCAM, ICAM-4 and LFA-3, both in percentage of positive cells and in surface density. (PMID:26137540)
• Frequent inactivating mutations of CD58 in classical Hodgkin lymphoma cell lines, but their rare occurrence in primary Hodgkin and Reed/Sternberg cells. (PMID:26194173)
• data suggest that loss of CD58 is a potential immune escape mechanism of HL tumor cells, especially in clinically aggressive disease (PMID:27467287)
• Mutations and copy number loss of CD58 or TP53 are identified to be an independent negative prognostic factors for diffuse large B cell lymphoma. (PMID:27825110)
• A new neuromyelitis optica spectrum disorders susceptibility variant was identified, rs56302466, on the CD58 gene, in a Han Chinese population. (PMID:28601281)
• indicate that including both CD58 and CD81 markers in addition to CD19, CD34, CD20, CD38, and CD10 are helpful in minimal residual disease detection by flow cytometry (PMID:29500862)
• SNP rs1335532 associated with multiple sclerosis is located in active CD58 enhancer region and creates a strong functional Ascl2-binding site. (PMID:30006149)
• High-resolution melting curve analysis of polymorphisms within CD58, CD226, HLA-G genes and association with multiple sclerosis susceptibility in a subset of Iranian population: a case-control study. (PMID:30128676)
• We show that the Alu insertion promotes skipping of CD58 exon 3 and results in a frameshifted transcript, indicating that the Alu may be the causative variant for increased MS risk at this locus. Using RT-PCR analysis at the endogenous locus, we confirm that the Alu variant is a sQTL for CD58. (PMID:30418605)
• Across different global populations and data sets, carriers of the multiple sclerosis risk allele showed reduced CD58 mRNA levels but increased hsa-miR-548ac levels. (PMID:30730892)

Cross-species orthologs

0 orthologs

Protein

Protein identifiers

Lymphocyte function-associated antigen 3 — P19256 (reviewed: P19256)

Alternative names: Surface glycoprotein LFA-3

All UniProt accessions (3): P19256, B1AMW1, H0YDI1

UniProt curated annotations — full annotation on UniProt →

Function. Ligand of the T-lymphocyte CD2 glycoprotein. This interaction is important in mediating thymocyte interactions with thymic epithelial cells, antigen-independent and -dependent interactions of T-lymphocytes with target cells and antigen-presenting cells and the T-lymphocyte rosetting with erythrocytes. In addition, the LFA-3/CD2 interaction may prime response by both the CD2+ and LFA-3+ cells.

Subunit / interactions. Interacts with CD2. Interacts with CMTM6. (Microbial infection) Interacts with human cytomegalovirus protein UL148; this interaction retains immature CD58 intracellularly.

Subcellular location. Cell membrane.

Miscellaneous. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

Isoforms (3)

UniProt ID	Names	Canonical?
P19256-1	1, Long	yes
P19256-2	2, Short
P19256-3	3

RefSeq proteins (2): NP_001138294, NP_001770* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR013783	Ig-like_fold	Homologous_superfamily
IPR015631	CD2/SLAM_rcpt	Family
IPR036179	Ig-like_dom_sf	Homologous_superfamily

UniProt features (35 total): strand 9, glycosylation site 6, mutagenesis site 6, splice variant 3, topological domain 2, helix 2, signal peptide 1, chain 1, disulfide bond 1, sequence variant 1, transmembrane region 1, turn 1, domain 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
1CCZ	X-RAY DIFFRACTION	1.8
1QA9	X-RAY DIFFRACTION	3.2
1CI5	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P19256-F1	83.54	0.55

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Disulfide bonds (1): 142–187

Glycosylation sites (6): 169, 195, 40, 94, 109, 135

Mutagenesis-validated functional residues (6):

Position	Phenotype
29	no effect on cd2-binding.
37	no effect on cd2-binding.
49	no effect on cd2-binding.
86	no effect on cd2-binding.
113	no effect on cd2-binding.
121	no effect on cd2-binding.

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-202733	Cell surface interactions at the vascular wall
R-HSA-6798695	Neutrophil degranulation
R-HSA-109582	Hemostasis
R-HSA-168249	Innate Immune System
R-HSA-168256	Immune System

MSigDB gene sets: 188 (showing top): RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, REACTOME_INNATE_IMMUNE_SYSTEM, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, GOBP_POSITIVE_REGULATION_OF_INTERLEUKIN_8_PRODUCTION, GOBP_RESPONSE_TO_PEPTIDE, GOCC_SECRETORY_GRANULE, MODULE_45, BOYAULT_LIVER_CANCER_SUBCLASS_G2, MODULE_493, GOCC_CELL_SURFACE, GOBP_POSITIVE_REGULATION_OF_CYTOKINE_PRODUCTION, GRANDVAUX_IRF3_TARGETS_DN, GOBP_CELL_CELL_ADHESION, WEI_MYCN_TARGETS_WITH_E_BOX, RICKMAN_METASTASIS_DN

GO Biological Process (6): immune response (GO:0006955), positive regulation of interleukin-8 production (GO:0032757), heterotypic cell-cell adhesion (GO:0034113), cellular response to type II interferon (GO:0071346), cellular response to tumor necrosis factor (GO:0071356), cell-cell adhesion (GO:0098609)

GO Molecular Function (2): signaling receptor binding (GO:0005102), protein binding (GO:0005515)

GO Cellular Component (6): plasma membrane (GO:0005886), cell surface (GO:0009986), membrane (GO:0016020), secretory granule membrane (GO:0030667), extracellular exosome (GO:0070062), ficolin-1-rich granule membrane (GO:0101003)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Hemostasis	1
Innate Immune System	1
Immune System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular response to cytokine stimulus	2
cellular anatomical structure	2
immune system process	1
response to stimulus	1
positive regulation of cytokine production	1
interleukin-8 production	1
regulation of interleukin-8 production	1
cell-cell adhesion	1
response to type II interferon	1
response to tumor necrosis factor	1
cell adhesion	1
protein binding	1
binding	1
membrane	1
cell periphery	1
secretory granule	1
cytoplasmic vesicle membrane	1
bounding membrane of organelle	1
extracellular vesicle	1
secretory granule membrane	1
tertiary granule	1
ficolin-1-rich granule	1

Protein interactions and networks

STRING

2212 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CD58	CD2	P06729	999
CD58	ICAM1	P05362	996
CD58	CD80	P33681	994
CD58	CD28	P10747	967
CD58	ITGAL	P20701	903
CD58	CD48	P09326	900
CD58	ITGB2	P05107	762
CD58	CD8A	P01732	756
CD58	CTLA4	P16410	736
CD58	CD40	P25942	722
CD58	CD276	Q5ZPR3	720
CD58	CD19	P15391	707
CD58	PTPRC	P08575	681
CD58	CD34	P28906	678
CD58	CD40LG	P29965	666

IntAct

27 interactions, top by confidence:

A	B	Type	Score
CD2	CD58	psi-mi:“MI:0915”(physical association)	0.710
CD58	CD2	psi-mi:“MI:0915”(physical association)	0.710
CD58	CD2	psi-mi:“MI:0407”(direct interaction)	0.710
LGALS3	PODXL	psi-mi:“MI:0914”(association)	0.530
PARP2	CD58	psi-mi:“MI:0557”(adp ribosylation reaction)	0.440
ABHD12B	CD58	psi-mi:“MI:0915”(physical association)	0.400
CD58	PTPRT	psi-mi:“MI:0915”(physical association)	0.400
ESR1	ESYT2	psi-mi:“MI:0914”(association)	0.350
CFTR	POTEF	psi-mi:“MI:0914”(association)	0.350
LGALS8	SLC22A23	psi-mi:“MI:0914”(association)	0.350
NUBP2	POTEF	psi-mi:“MI:0914”(association)	0.350
LGALS9	PODXL	psi-mi:“MI:0914”(association)	0.350
LGALS9	LGALS8	psi-mi:“MI:0914”(association)	0.350
HSPA12A	ARHGEF10	psi-mi:“MI:0914”(association)	0.350
LGALS8	NPC1	psi-mi:“MI:0914”(association)	0.350
AFG2A	ESYT2	psi-mi:“MI:0914”(association)	0.350
LGALS3	SDCBP	psi-mi:“MI:0914”(association)	0.350
LGALS9	CYB5A	psi-mi:“MI:0914”(association)	0.350
CFTR	UBA6	psi-mi:“MI:2364”(proximity)	0.270
CD58	DNAJA1	psi-mi:“MI:0915”(physical association)	0.000
HERPUD1	CD58	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (39): CD58 (Affinity Capture-MS), CD58 (Affinity Capture-MS), CD58 (Affinity Capture-MS), CD58 (Affinity Capture-MS), CD58 (Affinity Capture-MS), CD58 (Affinity Capture-MS), CD58 (Affinity Capture-MS), CD58 (Affinity Capture-MS), CD58 (Affinity Capture-MS), CD58 (Affinity Capture-MS), CD58 (Affinity Capture-MS), CD58 (Affinity Capture-MS), CD58 (Affinity Capture-MS), DNAJA1 (Two-hybrid), CD58 (Two-hybrid)

ESM2 similar proteins: A6QQC6, A8MVW5, B0CLX4, D3YX43, O00241, O18906, O54901, P04218, P05540, P06332, P09326, P0C788, P10252, P18181, P19256, P20273, P27931, P35329, P41217, P42071, P42081, P42082, P42292, P43303, P86176, Q00609, Q07763, Q15762, Q29037, Q4VAH7, Q501W4, Q5RAL8, Q5TFQ8, Q6GMZ9, Q7TSP5, Q8K4F0, Q8R2Y2, Q9D7L8, Q9D871, Q9EP73

SIGNOR signaling

0 interactions.

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: loss-of-function (tumor-suppressor-like) across 2 cancer types — DLBCLNOS, NHL.

Clinical variants and AI predictions

ClinVar

50 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	24
Likely benign	6
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

1089 predictions. Top by Δscore:

Variant	Effect	Δscore
1:116515282:C:CT	acceptor_gain	1.0000
1:116544306:CTCA:C	donor_loss	1.0000
1:116544307:TCA:T	donor_loss	1.0000
1:116544308:CAC:C	donor_loss	1.0000
1:116544309:ACC:A	donor_loss	1.0000
1:116544310:CCAAG:C	donor_gain	1.0000
1:116515282:C:T	acceptor_gain	0.9900
1:116544303:ATACT:A	donor_loss	0.9900
1:116544305:ACT:A	donor_loss	0.9900
1:116544309:A:AC	donor_gain	0.9900
1:116544309:AC:A	donor_gain	0.9900
1:116544310:C:CC	donor_gain	0.9900
1:116544310:CC:C	donor_gain	0.9900
1:116544310:CCA:C	donor_gain	0.9900
1:116544603:ACCT:A	acceptor_loss	0.9900
1:116544606:T:G	acceptor_loss	0.9900
1:116570896:CACT:C	donor_loss	0.9900
1:116570898:CTCA:C	donor_loss	0.9900
1:116570899:TCA:T	donor_loss	0.9900
1:116570900:C:CG	donor_loss	0.9900
1:116570901:A:AC	donor_gain	0.9900
1:116570901:A:T	donor_loss	0.9900
1:116570902:C:CC	donor_gain	0.9900
1:116570902:C:T	donor_loss	0.9900
1:116521898:ATAC:A	donor_loss	0.9800
1:116521899:TAC:T	donor_loss	0.9800
1:116521900:ACAT:A	donor_loss	0.9800
1:116521901:CA:C	donor_loss	0.9800
1:116521902:AT:A	donor_loss	0.9800
1:116521903:T:TG	donor_loss	0.9800

AlphaMissense

1647 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:116536116:C:A	W159C	0.995
1:116536116:C:G	W159C	0.995
1:116544507:C:A	W56C	0.993
1:116544507:C:G	W56C	0.993
1:116544367:T:G	Y103S	0.992
1:116544509:A:G	W56R	0.992
1:116544509:A:T	W56R	0.992
1:116536033:C:G	C187S	0.989
1:116536034:A:T	C187S	0.989
1:116544406:A:G	L90P	0.988
1:116544368:A:C	Y103D	0.987
1:116544368:A:G	Y103H	0.987
1:116544453:G:C	F74L	0.987
1:116544453:G:T	F74L	0.987
1:116544455:A:G	F74L	0.987
1:116536118:A:G	W159R	0.985
1:116536118:A:T	W159R	0.985
1:116544367:T:C	Y103C	0.985
1:116544508:C:G	W56S	0.985
1:116536168:C:G	C142S	0.980
1:116536169:A:T	C142S	0.980
1:116544485:C:G	A64P	0.977
1:116536034:A:G	C187R	0.976
1:116544406:A:T	L90H	0.976
1:116536169:A:G	C142R	0.975
1:116536167:G:C	C142W	0.971
1:116544487:A:T	V63D	0.971
1:116544400:A:C	I92S	0.970
1:116544368:A:T	Y103N	0.969
1:116544489:T:A	K62N	0.969

dbSNP variants (sampled 300 via entrez): RS1000060550 (1:116519706 T>C), RS1000062561 (1:116547991 A>G), RS1000141616 (1:116527921 C>A), RS1000152100 (1:116551251 C>T), RS1000175444 (1:116551657 T>C), RS1000284094 (1:116541640 T>C,G), RS1000291399 (1:116533436 T>C), RS1000336738 (1:116555132 A>G), RS1000426038 (1:116543615 C>G), RS1000515017 (1:116527548 T>C), RS1000635530 (1:116559033 A>G), RS1000801860 (1:116560935 A>C), RS1000857464 (1:116544029 A>G), RS1000858317 (1:116546636 C>A,T), RS1000943565 (1:116553519 G>A)

Disease associations

OMIM: gene MIM:153420 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

12 associations (top):

Study	Trait	p-value
GCST000424_1	Multiple sclerosis	3.000000e-10
GCST000425_1	Multiple sclerosis	1.000000e-07
GCST000949_3	Multiple sclerosis	1.000000e-07
GCST001198_9	Multiple sclerosis	3.000000e-16
GCST001341_3	Multiple sclerosis	6.000000e-09
GCST003566_8	Multiple sclerosis	2.000000e-12
GCST004302_19	Primary biliary cholangitis	2.000000e-12
GCST005531_102	Multiple sclerosis	5.000000e-42
GCST009597_77	Multiple sclerosis	5.000000e-70
GCST011096_1	Systemic lupus erythematosus	1.000000e-08
GCST011956_51	Systemic lupus erythematosus	3.000000e-13
GCST90011866_5	Systemic lupus erythematosus	3.000000e-10

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL3790 (SINGLE PROTEIN), CHEMBL3885600 (PROTEIN-PROTEIN INTERACTION)

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs12044852	Efficacy	3	interferon beta-1a;interferon beta-1b	Multiple Sclerosis

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs12044852	CD58	3	2.00	1	interferon beta-1a;interferon beta-1b

ChEMBL bioactivities

2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.16	IC50	6.9	nM	CHEMBL2153727
7.96	IC50	11.1	nM	CHEMBL2153728

PubChem BioAssay actives

2 with measured affinity, of 16 total; 2 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
2-[(3R,9S,12S,15S,18S,21S,24S,27S,30S,33S)-21-(4-aminobutyl)-15,24-bis[(2S)-butan-2-yl]-9,27-bis(carboxymethyl)-18-(hydroxymethyl)-12-[(4-hydroxyphenyl)methyl]-2,8,11,14,17,20,23,26,29,32-decaoxo-1,7,10,13,16,19,22,25,28,31-decazatricyclo[31.3.0.03,7]hexatriacontan-30-yl]acetic acid	689909: Inhibition of CD2-CD58 protein-protein interaction assessed as inhibition of cell adhesion between CD58 expressing human Caco2 cells and CD2 expressing human Jurkat cells by BCECF-AM fluorescent dye based fluorimetric assay	ic50	0.0069	uM
2-[(13S,16S,19S,22S,25S,28S)-19-(4-aminobutyl)-22-[(2S)-butan-2-yl]-13,16-bis(carboxymethyl)-25-[(4-hydroxyphenyl)methyl]-12,15,18,21,24,27,30-heptaoxo-2-oxa-11,14,17,20,23,26,29-heptazatetracyclo[31.4.0.03,8.04,37]heptatriaconta-1(33),3(8),4,6,34,36-hexaen-28-yl]acetic acid	689909: Inhibition of CD2-CD58 protein-protein interaction assessed as inhibition of cell adhesion between CD58 expressing human Caco2 cells and CD2 expressing human Jurkat cells by BCECF-AM fluorescent dye based fluorimetric assay	ic50	0.0111	uM

CTD chemical–gene interactions

61 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases methylation, affects cotreatment, increases expression	6
Benzo(a)pyrene	increases expression, increases methylation	4
Cyclosporine	increases expression	3
trichostatin A	affects expression, increases expression	2
sodium arsenite	affects cotreatment, decreases expression	2
entinostat	increases expression, affects cotreatment	2
Acetaminophen	decreases expression, increases expression	2
Arsenic	affects methylation, increases methylation	2
Cisplatin	decreases expression, increases expression	2
Estradiol	affects binding, increases reaction, decreases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Tretinoin	affects cotreatment, decreases expression, increases expression	2
Particulate Matter	decreases expression, increases expression	2
aristolochic acid I	decreases expression	1
triphenyl phosphate	affects expression	1
decabromobiphenyl ether	affects expression	1
beta-lapachone	increases expression	1
sulforaphane	increases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
N,N,N’,N’-tetrakis(2-pyridylmethyl)ethylenediamine	decreases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
perfluorooctane sulfonic acid	decreases expression	1
K 7174	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression, affects cotreatment	1
Grape Seed Proanthocyanidins	affects cotreatment, increases expression	1
pyrachlostrobin	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
jinfukang	decreases expression	1
picoxystrobin	increases expression	1
NSC 689534	affects binding, increases expression	1

ChEMBL screening assays

5 unique, capped per target: 3 binding, 2 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1023750	Binding	Inhibition of antiCD58-FITC binding to CD58 in human Caco-2 cells at 180 uM after 1 hr by fluorescence analysis relative to control	Design of beta-hairpin peptides for modulation of cell adhesion by beta-turn constraint. — J Med Chem
CHEMBL883847	Functional	Percent inhibition of E-rossette formation in sheep red blood cells at 200 uM on pre-incubation with T-cells	Structure-activity studies of peptides from the “hot-spot” region of human CD2 protein: development of peptides for immunomodulation. — J Med Chem

Cellosaurus cell lines

5 cell lines: 5 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B1MS	Abcam HeLa CD58 KO	Cancer cell line	Female
CVCL_B7WJ	Abcam Raji CD58 KO	Cancer cell line	Male
CVCL_B9X4	Abcam THP-1 CD58 KO	Cancer cell line	Male
CVCL_C6Z1	Abcam PC-3 CD58 KO	Cancer cell line	Male
CVCL_SH87	HAP1 CD58 (-)	Cancer cell line	Male

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.